Induction of Paracrine Signaling in Metastatic Melanoma Cells by PPARγ Agonist Rosiglitazone Activates Stromal Cells and Enhances Tumor Growth.

Pich, Christine; Meylan, Patrick; Mastelic-Gavillet, Beatris; Nguyen, Thanh Nhan; Loyon, Romain; Trang, Bao Khanh; Moser, Hélène; Moret, Catherine; Göpfert, Christine; Hafner, Jürg; Levesque, Mitchell P; Romero, Pedro; Jandus, Camilla; Michalik, Liliane (2018). Induction of Paracrine Signaling in Metastatic Melanoma Cells by PPARγ Agonist Rosiglitazone Activates Stromal Cells and Enhances Tumor Growth. Cancer research, 78(22), pp. 6447-6461. American Association for Cancer Research AACR 10.1158/0008-5472.CAN-18-0912

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In addition to improving insulin sensitivity in type 2 diabetes, the thiazolidinedione family of compounds and the pharmacologic activation of their best-characterized target PPARγ have been proposed as a therapeutic option for cancer treatment. In this study, we reveal a new mode of action for the thiazolidinedione rosiglitazone that can contribute to tumorigenesis. Rosiglitazone activated a tumorigenic paracrine communication program in a subset of human melanoma cells that involves the secretion of cytokines, chemokines, and angiogenic factors. This complex blend of paracrine signals activated nonmalignant fibroblasts, endothelial cells, and macrophages in a tumor-friendly way. In agreement with these data, rosiglitazone promoted human melanoma development in xenografts, and tumors exposed to rosiglitazone exhibited enhanced angiogenesis and inflammation. Together, these findings establish an important tumorigenic action of rosiglitazone in a subset of melanoma cells. Although studies conducted on cohorts of diabetic patients report overall benefits of thiazolidinediones in cancer prevention, our data suggest that exposure of established tumors to rosiglitazone may be deleterious. These findings uncover a novel mechanism by which the thiazolidinedione compound rosiglitazone contributes to tumorigenesis, thus highlighting a potential risk associated with its use in patients with established tumors. .

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Göpfert, Christine

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0008-5472

Publisher:

American Association for Cancer Research AACR

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

20 May 2019 16:06

Last Modified:

24 Oct 2019 21:18

Publisher DOI:

10.1158/0008-5472.CAN-18-0912

PubMed ID:

30185551

BORIS DOI:

10.7892/boris.127543

URI:

https://boris.unibe.ch/id/eprint/127543

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